The mechanisms of the biosynthesis of nerve growth factor (NGF) and of the two other subunits with which it is associated in the high molecular weight complex will be explored in in vitro incorporation experiments in submaxillary gland slices and in cell-free synthesizing systems translating RNA from the gland. The identity of the primary translation product of the NGF gene and the specificity of its processing will be examined. The interaction of NGF with its specific receptors on sympathetic and sensory neurons will be compared with the interactions on PC12 cells. The time course of the internalization of NGF and of its lysosomal degradation or transport to the nucleus will be determined for PC12 cells in suspension and on plates. Attempts will be made to correlate nuclear binding with initiation of neurite outgrowth and to characterize the way in which cyclic AMP is partly able to mimic NGF.